Key Facts

Neonatal sepsis remains a significant cause of neonatal mortality and morbidity. The non-specific nature of neonatal sepsis signs makes a high index of suspicion essential. NICE CG149 provides a structured approach based on risk factors and clinical indicators.

Epidemiology

EONS incidence: ~0.9 per 1,000 live births. GBS-EONS: ~0.5 per 1,000. LONS is more common in preterm infants, especially those with central venous lines. Neonatal sepsis mortality: ~5-10% for term infants, up to ~30% for very preterm.

Aetiology

Early-onset (<72h):

• Group B Streptococcus (GBS) - most common overall
• Escherichia coli - most common Gram-negative; leading cause in preterm EONS
• Listeria monocytogenes - uncommon but important (maternal food-borne)

Late-onset (72h-28 days):

• Coagulase-negative Staphylococci (CoNS) - most common in NICU (line-related)
• Staphylococcus aureus, E. coli, Klebsiella, Candida (very preterm)

Pathophysiology

Neonatal immune system is immature: reduced complement activity, low IgM and IgA (only maternal IgG crosses placenta), impaired neutrophil chemotaxis and opsonisation, and reduced T-cell function. This renders neonates highly susceptible to bacterial infection with rapid progression to septic shock and meningitis.

Clinical Signs (Non-Specific)

• Temperature: Hypothermia (<36°C) or fever (>38°C); hypothermia more common in preterm
• Respiratory: Tachypnoea, grunting, apnoeas, increased O2 requirement
• Cardiovascular: Tachycardia, poor perfusion, hypotension (late sign)
• Neurological: Lethargy, irritability, poor feeding, seizures, bulging fontanelle
• GI: Feeding intolerance, abdominal distension, vomiting
• Skin: Mottling, pallor, petechiae, prolonged CRT

NICE CG149 Risk Factors for EONS

Red flags (treat immediately):

• Clinical signs of neonatal sepsis
• Suspected or confirmed maternal sepsis treated with IV antibiotics
• Maternal GBS colonisation + ONE of: preterm labour, PROM >18h, maternal fever >38°C

Non-red flag risk factors (observe ± treat):

• PROM >18h, maternal GBS colonisation (without additional risk factors), maternal pyrexia, gestational age <37 weeks

Red Flags

• Apnoeas - may be only sign of sepsis in preterm infants
• Seizures - suggests meningitis
• Rapidly deteriorating - fulminant sepsis/meningitis
• Purpura/petechiae - DIC, meningococcal (rare in neonates)

Bedside

• Observations: Temperature, HR, RR, SpO2, BP, capillary refill
• Blood glucose: Hypoglycaemia common in sepsis

Bloods

• Blood culture: GOLD STANDARD - before antibiotics if possible (but do NOT delay antibiotics)
• FBC: WCC may be high, low, or normal; left shift (raised immature:total neutrophil ratio); thrombocytopenia
• CRP: May be normal initially; repeat at 18-24h (serial CRP is useful)
• Procalcitonin: Rising - more specific than CRP for bacterial infection
• Blood gas: Metabolic acidosis in severe sepsis

Imaging

• CXR: If respiratory symptoms - pneumonia, RDS
• AXR: If abdominal signs - NEC

Special Tests

• LP (CSF): For all confirmed sepsis or strong clinical suspicion of meningitis - cell count, protein, glucose, culture, PCR
• Urine MC&S: More relevant in LONS (clean catch or SPA)
• Surface swabs: Ear, umbilicus - may guide therapy but not diagnostic of invasive infection

Pharmacological

EONS (<72h):

• IV benzylpenicillin 25mg/kg 12-hourly (term; 8-hourly if meningitis) + gentamicin 5mg/kg OD
• Start within 1 hour of decision to treat
• Duration: Stop at 36-48h if blood culture negative AND clinically well AND CRP not rising
• If culture positive or meningitis confirmed: Continue for 7-14 days (meningitis: 14-21 days depending on organism)

LONS (>72h):

• Flucloxacillin + gentamicin (or per local protocol if NICU-acquired - may need broader cover)
• Candida: Fluconazole or amphotericin B for very preterm infants

Meningitis:

• Extend to meningitis doses: Benzylpenicillin or cefotaxime 50mg/kg + gentamicin
• Duration: GBS meningitis 14 days; Gram-negative meningitis 21 days

Non-pharmacological

• IV access: Ensure reliable venous access
• Fluid resuscitation: 10-20mL/kg 0.9% NaCl bolus if signs of shock; may need inotropes
• Respiratory support: CPAP, IPPV as needed
• Monitoring: Continuous cardiorespiratory monitoring, fluid balance, blood glucose
• Nutritional support: May need parenteral nutrition if feeds withheld

Referral Criteria

• All unwell neonates - neonatal team assessment
• Meningitis - neonatal unit; may need neurosurgical input if complications
• Not responding to first-line antibiotics - microbiology/infectious disease input
• Preterm LONS - neonatal unit

• EONS (GBS) mortality: ~5-10% in term infants; higher in preterm
• Gram-negative EONS mortality: ~15-20%
• GBS meningitis: Mortality ~10%; long-term neurodevelopmental sequelae in ~50% of survivors
• LONS (CoNS): Low mortality (<5%) but associated with prolonged NICU stay
• CRP as guide: Serial CRP helps guide antibiotic duration; falling CRP supports stopping at 36-48h if culture negative

NICE CG149 - Decision Framework

Antibiotic Doses (Neonatal)